factor viia for emergent warfarin reversal david pavlik, pharm.d. clinical specialist –...

Factor VIIa for

Emergent Warfarin Reversal

David Pavlik, Pharm.D.Clinical Specialist – Trauma/Critical Care

Allegheny General HospitalPittsburgh, PA

PSHP Annual Assembly – October 1st, 2008

Disclosures / Conflict of Interest

• None

ObjectivesObjectives• Review warfarin-related pharmacology Review warfarin-related pharmacology • Evaluate available options for warfarin reversalEvaluate available options for warfarin reversal• Evaluate Factor VIIa pharmacology and Evaluate Factor VIIa pharmacology and

pharamcokineticspharamcokinetics• Summarize Factor VIIa literature for warfarin reversalSummarize Factor VIIa literature for warfarin reversal• Compare PCC to rVIIa for warfarin reversalCompare PCC to rVIIa for warfarin reversal

Warfarin—Mechanism of ActionWarfarin—Mechanism of Action

Vitamin KVitamin K

WarfarinWarfarin

Synthesis of Dysfunctional Synthesis of Dysfunctional Coagulation FactorsCoagulation Factors

VIIVII

IXIXXXIIII

Vitamin K Utilization Reduced

Diagram adapted from www.factorviia.com

Vitamin KVitamin K

• Required for prolonged reversal of warfarin

• Order in most cases of severe warfarin-related bleeding

Warfarin Related BleedingWarfarin Related Bleeding

ACCP – Serious/Life Threatening Bleed

• Hold Warfarin• Vitamin K

• Fresh Frozen Plasma OR• Prothrombin Complex OR• Factor VIIa

Ansell et al. CHEST 2008;133:160S

Fresh Frozen Plasma (FFP)• Volume Concerns

• INR = 2.5 then dose ~1600mL or 4-6 Units• INR > 5 then dose ~2800mL or 8-10 Units

• Infusion Time

• Factor concentrations variable• Delays in obtaining product

Aguilar M et al Mayo Clin Proc 2007; 82(1):82-92

Schulman et al N Engl J Med 2003; 349;675-83

Factor VIIa - Indications

• Hemophilia A or B with Inhibitors to Factors VIII or IX

• 90 mcg/kg every 2 hours as needed

• Factor VII deficiency• 15-30 mcg/kg every 4-6 hours as needed

Factor VIIa Off-Label

• Massive Transfusion• Trauma• Cardiothoracic Surgery

• Coagulopathy• Liver Disease/Transplant• Hematologic Disorders• Warfarin

TF-Bearing CellTF-Bearing Cell

VaVaTFTF VIIaVIIa XaXa

XX IIIIIIaIIa VIII/vWFVIII/vWF

VIIIaVIIIa

VV VaVa

PlateletPlatelet

TFTFIXIX

IXaIXa

Activated PlateletActivated Platelet

Coagulation PathwayCoagulation Pathway

XX

XaXaVIIIaVIIIaIXaIXa

Adapted from: Hoffman et al. Adapted from: Hoffman et al. Blood Coagul FibrinolysisBlood Coagul Fibrinolysis 1998;9(suppl 1):S61. 1998;9(suppl 1):S61.

VIIaVIIa

Alternate Mechanism

Activated PlateletActivated Platelet

XXXaXa

IIaIIaIIII

Recombinant Factor VIIaRecombinant Factor VIIabinding to activated plateletsbinding to activated platelets

Allen Can J Anesth 2002;49(10):S7-S14

VIIa

Factor VIIa - Kinetics

• Onset• 10-20 minutes

• Infusion volume <10mL

• Half-Life• 2.5 hours

• Recombinant Product

CCostost

Agent Cost

Fresh Frozen Plasma (4-6 Units) $300-500

Prothrombin Complex 2000 Units $1020-1620

Prothrombin Complex 3000 Units $1530-2430

Factor VIIa 1-2mg (~15-20mcg/kg) $1100-2200

Factor VIIa 3-4mg (~40mcg/kg) $3300-4500

Factor VIIa 6-7mg (~90mcg/kg) $6500-8000

Deveras et al.

• Reported 13 patients on warfarin• Doses

• 12-90 mcg/kg• 8 with 1.2mg (12-25 mcg/kg)

• Indications• Supratherapeutic INR/High risk of bleed• Rapid reversal required• Invasive procedures• Bleeding

Deveras Ann Int Med 2002; 137:884-888

Deveras - Low-Dose rFVIIa

Patient Indication Dose

mcg/kg (mg)

Pre-INR Post-INR

55F Bleeding 20 (1.2) 13.9 5.6

41M Procedure 14 (1.2) 3.4 1.7

56M Bleeding 14 (1.2) 5.8 2.9

38M High Risk 15 (1.2) 6.2 2.1

74M Procedure 12 (1.2) 2.6 1.6

73F Procedure 17 (1.2) 1.9 0.7

44M High Risk 15 (1.2) 11.9 3.2

81F High Risk 25 (1.2) 8.9 3.2

ICH on Warfarin

Author N Adjunct Agents Dose(mcg/kg)

Outcome

Sorenson 7 FFP in 5/7Platelets in 1/7Vitamin K in 6/7

10-40 Hemostasis

Lin 4 FFP in 4/4 16-22 1 Death3 Recover

Veschev 1 Not stated 120 Death

Dutton 9 Not stated 36-152 5 Death4 Discharged

Freeman 7 FFP + Vit K in 8/9 15-90 2 Death5 GCS=3

Dager et al.• 16 warfarin patients with major bleeding

• 12 CNS bleeding/Neurosurgery• 3 Retroperitoneal bleeding• 1 emergent reversal for bleeding during

laparotomy

• Fixed dose of 1.2 mg• Mean = 16 mcg/kg (11-25mcg/kg)

• All received FFP• 13/16 received Vitamin K

Dager et al. Pharmacotherapy 2006;26(8):1091-98

Dager et al - Results

• Pre Dose INR• 2.8±1.6 (1.39-6.34)

• Post Dose INR• 1.1± 0.3 (0.86-1.92)• Mean = 35 minutes (10-165)• 15/16 had INR <1.4• 8/16 had INR<1

• Satisfactory Hemostasis in 14/16

Ilyas et al. – Warfarin related ICH

30 Factor VIIa vs 24 historical controls Factor VIIa doses ranging from 10-100mcg/kg Historical controls received FFP “Most” received vitamin K

Results Time to INR <1.4 (2.4 vs 13.7 hours)

– Mean =0.6 with Factor VIIa

Reduced plasma use (4 vs 7.7 units) One myocardial infarction temporally related to

Factor VIIa

Ilyas et al. J Clin Anesth (2008):20,276-79

Ilyas et al.

Thrombotic Events - Factor VIIaThrombotic Events - Factor VIIa

Hemophlia 1-2 %

Trauma Study 3-6 %

ICH Study

Arterial Events

9-10%

9 vs 4%

CT Surgery 16 %

Warfarin Reversal ??

Levi Crit Care Med 2005;33(4):883 Boffard J Trauma 2005;59:8-18

Mayer N Eng J Med 2008; 358:2127 Karkouti Transfusion 2005;45:26-34.

PCC Disadvantages

• Extended half-lives• Factor II (60hrs)• Factor X (30hrs)

• Availability

• Viral Transmission

• Optimal dose/methodology unclearSorenson et al. Blood Coagl Fibrinolysis 2003 12:469-77


AGH PCC Dosage CalculationAGH PCC Dosage Calculation

• Factor Desired• Use ≥ 60% to reverse bleeding• Use ≥ 90% to reverse bleeding in patients in need

of urgent surgical procedures

• Factor Observed

Patient Patient Weight Weight

(kg)(kg)XX

70 mL 70 mL Blood/kgBlood/kg XX 1-HCT%1-HCT% XX

%%

Factor Factor DesiredDesired

--% %

Factor Factor ObservedObserved

*If INR is unavailable weight based dosing may be utilized (35 IU/kg)

Factor ObservedFactor ObservedINRINR Factor %Factor %

1.01.0 9090

1.51.5 4545

2.02.0 3737

2.52.5 3030

3.03.0 2323

3.53.5 2020

4.04.0 1515

6.06.0 12.512.5

9.59.5 1010

10.010.0 55

So easy Korczynski can do it!

AGH PCC Dosage CalculationAGH PCC Dosage Calculation Weight (kg)Weight (kg) Hematocrit %Hematocrit % Factor DesiredFactor Desired

Level of factors needed to be replacedLevel of factors needed to be replaced Use ≥ 60% to reverse bleedingUse ≥ 60% to reverse bleeding Use ≥ 90% to reverse bleeding in patients in need of urgent Use ≥ 90% to reverse bleeding in patients in need of urgent

surgical proceduressurgical procedures Factor ObservedFactor Observed

Using reported INR and Factor Observed TableUsing reported INR and Factor Observed Table


(kg)(kg)XX

70 mL 70 mL Blood/kgBlood/kg XX 1-HCT% 1-HCT%

%%


--% %



X

PCC - Disadvantages

• Variable Factor Content by brand• Units/vial may vary by lot


35

Conclusions

• Factor VIIa is an option for emergent warfarin reversal

• Optimal use not fully defined• Dose• Monitoring

• Large scale clinical trials are lacking

Prothrombin Complex Concentrates (PCC)for


Michael Korczynski Pharm.D.Clinical Specialist – Ambulatory Care


PSHP Annual Assembly – October 1st, 2008

DisclosuresDisclosures• NoneNone

ObjectivesObjectives• Review of warfarin-related bleeding riskReview of warfarin-related bleeding risk• Evaluate available options for warfarin reversalEvaluate available options for warfarin reversal• Examine PCC CharacteristicsExamine PCC Characteristics• Summarize PCC literatureSummarize PCC literature• Compare PCC to rVIIa for warfarin reversalCompare PCC to rVIIa for warfarin reversal

Warfarin and bleeding riskWarfarin and bleeding risk• Most common complication is bleedingMost common complication is bleeding

• Incidence can range from 5-50%Incidence can range from 5-50%• Related to intensity of anticoagulationRelated to intensity of anticoagulation• Risk factorsRisk factors

• Age > 65 yearsAge > 65 years• Age > 75 years with concomitant afib/ICHAge > 75 years with concomitant afib/ICH• History of GI bleedingHistory of GI bleeding• Comorbid disease states:Comorbid disease states:

• Hypertension Hypertension • Cerebrovascular diseaseCerebrovascular disease• Serious heart disease Serious heart disease • Renal insufficiencyRenal insufficiency

Am Fam Physician. 1999 Feb 1;59(3):635-46

Warfarin and Intracranial Hemorrhage (ICH)Warfarin and Intracranial Hemorrhage (ICH)

• Overall increases the risk of ICH 2-5xOverall increases the risk of ICH 2-5x• Depends on anticoagulation intensityDepends on anticoagulation intensity• Estimated to account for about 3500 ICHs annuallyEstimated to account for about 3500 ICHs annually• ~ 5 % of all non-traumatic ICH episodes ICH in the US~ 5 % of all non-traumatic ICH episodes ICH in the US• Spontaneous ICH among 70-year-olds averages 0.15 % Spontaneous ICH among 70-year-olds averages 0.15 %

per yearper year• Those closely monitored on warfarin (INR of 2- 3), risk Those closely monitored on warfarin (INR of 2- 3), risk

of ICH increases to 0.3 to 0.8 percent/yearof ICH increases to 0.3 to 0.8 percent/year

.

Options for Emergent Warfarin ReversalOptions for Emergent Warfarin Reversal

Agent

Factor

Content Volume Onset Duration Cost

IV

Vitamin K

None Minimal ~1-2 hours ~12-14 hours

$

FFP

All cont. in normal

human

plasma*

1-2 liters

(4-6 units) immediate ~24 hours

$$

rVIIa rVIIa minimal immediate ~2 hours

$$$

PCC II, VII, IX, X 60-100ml immediate ~24 hours

$$$

*may contain lower levels of factor IX, and VIII than normal human plasma

PCCPCC

• Pooled-plasma product from live donorsPooled-plasma product from live donors• Contains vitamin K dependent clotting Contains vitamin K dependent clotting

factors II, VII, IX, and Xfactors II, VII, IX, and X• FDA approved for the prevention and FDA approved for the prevention and

control of hemorrhagic episodes in control of hemorrhagic episodes in hemophilia B patientshemophilia B patients

• Literature reports for warfarin reversalLiterature reports for warfarin reversal

Baxter, Bebulin VH® (Package Insert)

New Product?New Product?

• Around since the early 1990’sAround since the early 1990’s• Concern of viral transmission Concern of viral transmission • More sophisticated purification More sophisticated purification

processes have reduced viral riskprocesses have reduced viral risk• Effective in correcting the INR and Effective in correcting the INR and

stopping bleedingstopping bleeding• Must be combined with Vitamin KMust be combined with Vitamin K

Bebulin VH®Bebulin VH®

• Vapor heat treated• Unit content differs between lots • Contains lyophilized powder and diluent• Must be refrigerated prior to mixing• Use within 3 hours of reconstitution• Infuse at ≤ 3ml/min

Product Factor II

Factor VII

Factor IX

Factor X

Bebulin VH 120 13 100 139

Baxter, Bebulin VH® (Package Insert)

Why PCC?Why PCC?

• PCC contains in clotting factors:PCC contains in clotting factors:• II (prothrombin), VII, IX, and X.II (prothrombin), VII, IX, and X.

• Warfarin depletes clotting factors:Warfarin depletes clotting factors:• II (prothrombin), VII, IX, and XII (prothrombin), VII, IX, and X

• Quick onset of action (15-30 minutes)Quick onset of action (15-30 minutes)• Long duration of action (~24 hours)Long duration of action (~24 hours)• Factor VIIa does not supplement all Factor VIIa does not supplement all

coagulation factors coagulation factors • Short half-life (~2.5 hours) Short half-life (~2.5 hours)

• CHEST GuidelinesCHEST Guidelines

General Usage ConsiderationsGeneral Usage Considerations

• Patients and families may object to PCC (a Patients and families may object to PCC (a pooled plasma product) or rVIIa on religious pooled plasma product) or rVIIa on religious grounds. grounds.

• PCC should only be used if traditional PCC should only be used if traditional modalities to correct warfarin related modalities to correct warfarin related bleeding are insufficient to work in a timely bleeding are insufficient to work in a timely mannermanner

• Patients at high risk for thrombosisPatients at high risk for thrombosis• Active ischemic diseaseActive ischemic disease• Mechanical heart valvesMechanical heart valves• Antiphospholipid antibody syndrome (APLS)Antiphospholipid antibody syndrome (APLS)

PCC CharacteristicsPCC Characteristics

Pros

Rapid reversal of INRRapid reversal of INR

Standardized coagulation factor Standardized coagulation factor componentscomponents

Limited volumeLimited volume

One-time dosingOne-time dosing

↓↓ risk of virus transmissionrisk of virus transmission

Cons

Limited dataLimited data

Cost (~$500/vial)Cost (~$500/vial)

Potential thrombosis riskPotential thrombosis risk

Lack of consensus on dosingLack of consensus on dosing

ACCP Management of Elevated INRsACCP Management of Elevated INRs

Life-Threatening Bleeding

Hold warfarinHold warfarin

Give FFP, PCC, or rVIIaGive FFP, PCC, or rVIIa

Supplement with vitamin K Supplement with vitamin K (10mg by slow IV infusion)(10mg by slow IV infusion)

Repeat, if necessary, Repeat, if necessary, depending on INRdepending on INR

Serious Bleeding at any elevation of INR

Hold warfarinHold warfarin

Vitamin K (10 mg by slow IV Vitamin K (10 mg by slow IV infusion); can be repeated infusion); can be repeated q12h q12h

Supplemented with FFP, PCC, Supplemented with FFP, PCC, or rVIIa, depending on the or rVIIa, depending on the urgency of the situationurgency of the situation

CHEST 2008

Literature ReviewLiterature Review

• Use for warfarin reversal has been Use for warfarin reversal has been documented:documented:

• Small prospective and retrospective Small prospective and retrospective studiesstudies

• Case reportsCase reports• Primary objective of most studies was to Primary objective of most studies was to

determine the efficacy of PCC based on INR determine the efficacy of PCC based on INR reversalreversal

• Various dosing regimens have be utilizedVarious dosing regimens have be utilized

Throb Res. 2005:115(6):455-9

Ann Hematol. 2003:8(2):121-3

Br J Haematol. 2002:116(3):619-24

Hematology 2001: 115:998-1001

Literature ReviewLiterature Review

Yasaka1: 42 patients; PCC ± Vit K

Dose IU 200 500

1000

1500

INR Reduction 3.4-1.1

2.5-1.2

2.2-0.9

2.3-0.9

Yasaka2: 17 patients

Group PCC Only

PCC/

Vit. K

Vitamin K Only

Median Dose

500 IU 7-27 IU/kg + 10 mg

10-20mg

INR Reduction

6.2-2.1 2.7-1.1 2.7-1.3

Preston3: 42 patients; Dose based on INR

Baseline INR 2-3.9 4-6 >6

Dose (IU/kg) 25 35 50

Evans4: 10 patients; INRs >8

Dose (PCC and Vitamin K)

30 IU/kg + 5mg

Median INR Reversal

20-1.1

1 Throb Res. 2005:115(6):455-9 2 Ann Hematol. 2003:8(2):121-33 Br J Haematol. 2002:116(3):619-24 4 Hematology 2001: 115:998-1001

Literature ReviewLiterature ReviewLorenz1: 8 patients; PCC only fixed dose

Dose IUDose IU 36003600

INR INR ReductionReduction 3.4-1.33.4-1.3

Reiss2: 56 patients; PCC only weight-based

Dose IU/kgDose IU/kg 41.141.1/kg

INR INR

ReductionReduction 2.8-1.12.8-1.1

Lankiewicz3: 88 patients; PCC only weight-based

Dose IU Dose IU 25-50/kg25-50/kg

INR INR ReductionReduction 3.8-1.33.8-1.3

1 Blood Coagul Fibrinolysis. 2007 Sep;18(6):565-70 2 Thromb Res. 2007;121(1):9-16 3 J Thromb Haemost. 2006 May;4(5):967-70 4 J Thromb Haemost. 2008 Apr;6(4):622-31

Pabinger4: 43 patients; dosed based on weight and INR

Baseline INRBaseline INR 2-3.92-3.9 4-64-6 >6>6

Dose (IU/kg)Dose (IU/kg) 2525 3535 5050

PCC AdvantagesPCC Advantages

• Known factor contentKnown factor content• Low volumeLow volume• Contains factors II, VII, IX, XContains factors II, VII, IX, X• Rapid administrationRapid administration• Long duration of effect (~24 hours)Long duration of effect (~24 hours)• Only one dose requiredOnly one dose required

• Average dose: $1500Average dose: $1500• Dosing optionsDosing options

• Fixed dosingFixed dosing• Weight/INR Weight/INR • Factor replacementFactor replacement

PCC ConcernsPCC Concerns

• Risk of thrombosisRisk of thrombosis• Low risk of virus transmissionLow risk of virus transmission

• Hepatitis CHepatitis C• ParvovirusParvovirus

• Infusion reactionsInfusion reactions• CostCost

• $1500/dose$1500/dose

rVIIa CharacteristicsrVIIa Characteristics

• Contains only factor rVIIaContains only factor rVIIa• Short half-life (~2.5 hours)Short half-life (~2.5 hours)• May require multiple doses ($$$)May require multiple doses ($$$)

• 1mg = ~$11001mg = ~$1100• Limited literature support for warfarin reversalLimited literature support for warfarin reversal• No consistent approach to dosingNo consistent approach to dosing

Factor VIIa - Dose vs. Duration

– 5-20 mcg/kg– Duration ~4-8hrs– Cost~$1,100-2,200

– 40-80 mcg/kg– Duration ~10-12 hrs– Cost~$3,300-6,600

– 120-320mcg/kg– Duration ~18-20 hrs– Cost ~$9,900-25,600

Girard et al. Thromb Hemost 1998;80:109-13

Placebo

PCC vs rVIIaPCC vs rVIIa • In vivo rat and in vitro human modelsIn vivo rat and in vitro human models • Compared recovery of endogenous thrombin Compared recovery of endogenous thrombin

generationgeneration• Rats received phenprocoumon Rats received phenprocoumon • Humans received warfarinHumans received warfarin• Plasma samples from warfarin-treated individualsPlasma samples from warfarin-treated individuals

• INR values of 2.1-6.7INR values of 2.1-6.7• Treatments evaluated using prothrombin time (PT) Treatments evaluated using prothrombin time (PT)

and thrombin generation measurementand thrombin generation measurement• PCC and rFVIIa reverse warfarin anticoagulation PCC and rFVIIa reverse warfarin anticoagulation

based on PTbased on PT• Only PCC restored overall thrombin generation Only PCC restored overall thrombin generation

Tanaka KA, et al. Thromb Res. 2008;122(1):117-23

Antifibrinolytic ActivityAntifibrinolytic Activity

• PCC and rVIIa added to plasma PCC and rVIIa added to plasma samples of warfarin-treated patientssamples of warfarin-treated patients

• PCC was more effective in increasing PCC was more effective in increasing thrombin compared to rVIIathrombin compared to rVIIa

• Warfarin activity dependent on reduced Warfarin activity dependent on reduced prothrombin activityprothrombin activity rather than factor VII

• Thrombin activity measured by Thrombinoscope system

Taketomi et al. Blood Coagul Fibrinolysis. 2008 Jan;19(1):106-8.Taketomi et al. Blood Coagul Fibrinolysis. 2008 Jan;19(1):106-8.

Risk of Adverse EventsRisk of Adverse Events

• All patients on warfarin have inherent risk of All patients on warfarin have inherent risk of thrombosisthrombosis

• Low risk of virus transmission with PCCLow risk of virus transmission with PCC• Use in emergent/life-threatening situationsUse in emergent/life-threatening situations• Cost/benefit analysisCost/benefit analysis• Is rapid correction necessary?Is rapid correction necessary?• Monitor for signs/symptoms of PE, DVT, MI, Monitor for signs/symptoms of PE, DVT, MI,

strokestroke

PCC Ordering ProtocolPCC Ordering Protocol• First doses MUST be ordered under the approval of an First doses MUST be ordered under the approval of an

attending physician for warfarin reversal ONLY. attending physician for warfarin reversal ONLY. • First doses require subsequent consultation with the First doses require subsequent consultation with the

Hematology attending on-call.Hematology attending on-call.• Only one dose will be ordered at a timeOnly one dose will be ordered at a time• One dose should be sufficientOne dose should be sufficient• If a second is requested, then consultation with the If a second is requested, then consultation with the

hematology/anticoagulation service is required.hematology/anticoagulation service is required.• Doses will be rounded to the nearest vial size. Vial size Doses will be rounded to the nearest vial size. Vial size

can vary from depending on product and lot availabilitycan vary from depending on product and lot availability • All patients must receive Vitamin K 10 mg IV mixed in All patients must receive Vitamin K 10 mg IV mixed in

50mL NSS via slow infusion (over 30 minutes) along with 50mL NSS via slow infusion (over 30 minutes) along with PCCPCC

PCC Ordering ProtocolPCC Ordering Protocol

• Criteria for use:Criteria for use:• INR ≥ 2.5 INR ≥ 2.5 • Serious or life-threatening bleeding Serious or life-threatening bleeding

• Immediate reversal of warfarinImmediate reversal of warfarin• Immediate reversal of warfarin prior to an urgent Immediate reversal of warfarin prior to an urgent

neurosurgical procedureneurosurgical procedure• If above criteria not met PCC should not If above criteria not met PCC should not

be dispensedbe dispensed

AGH PCC Dosage CalculationAGH PCC Dosage Calculation Weight (kg)Weight (kg) Hematocrit %Hematocrit % Factor DesiredFactor Desired

Level of factors needed to be replacedLevel of factors needed to be replaced Use ≥ 60% to reverse bleedingUse ≥ 60% to reverse bleeding Use ≥ 90% to reverse bleeding in patients in need of urgent Use ≥ 90% to reverse bleeding in patients in need of urgent

surgical proceduressurgical procedures Factor ObservedFactor Observed

Using reported INR and Factor Observed TableUsing reported INR and Factor Observed Table


(kg)(kg)XX

70 mL 70 mL Blood/kgBlood/kg XX 1-HCT% 1-HCT%

%%


--% %



X

PCC CalculatorPCC Calculator

PCC- Conclusions

• Emerging literature advocating PCC use in emergent warfarin reversal

• Dosing methods available:• Fixed dosing• Weight based dosing• Factor replacement dosing

• Large scale clinical trials lacking

Final Thoughts

Factor VIIa- possible uses for warfarin

• Emergent reversal• Serious/Life threatening bleeding• Reversal for emergent surgery

• Patients unable to receive blood products

• Other factor shortage• PCC, FFP

• At risk for circulatory overload

Factor VIIa - Dosing

• INR <4*• 15-20mcg/kg

• INR >4*• 40mcg/kg

*INR may not represent full factor repletion

• Standard therapy• FFP• Vitamin K

• Consider omission of Factor VIIa if FFP can be given in a timely fashion

PCC’s Role

Recommended• Life-threatening Life-threatening

bleeding bleeding on on warfarinwarfarin

• Patient cannot Patient cannot handle large handle large volumes volumes

• Supratherapeutic Supratherapeutic INRsINRs

Not Recommended• Non-warfarin related Non-warfarin related

coagulopathycoagulopathy• Failure to reverse Failure to reverse

warfarin prior to warfarin prior to surgerysurgery

PCC/Factor VIIa - where NOT to use

• Active/recent ischemia or thrombosis• Hypercoaguable state

• APLS• Non-coagulopathic bleeding

• Spontaneous ICH• Minor bleeding• Elective Procedures• Overlapping DIC/Sepsis ?• Liver failure (PCC)

Mayer et al. N Engl J Med 2008;358:2127

Broderick et al. Stroke 2007;38:2001

Prothrombin Complex Concentrates (PCC)and Factor VIIa for


Michael Korczynski Pharm.D.Clinical Specialist – Ambulatory Care

David Pavlik, Pharm.D.Clinical Specialist- Trauma/Critical Care


factor viia for emergent warfarin reversal david pavlik, pharm.d. clinical specialist –...

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